National Cancer Institute (NCI) scientists have discovered how human T-cell leukemia virus type 1 (HTLV-1), which infects about 20 million people worldwide, evades being held in check by one of the body's natural defense mechanisms. An active infection with HTLV-1 leads to T-cell leukemia in up to five percent of all cases worldwide. NCI is part of the National Institutes of Health.
The study, appearing online the week of February 5, 2007 in the Proceedings of the National Academy of Sciences (PNAS), details how an enzyme, called either APOBEC3G or hA3G, is prevented from being packaged into virus particles and thus can not perform its normal function of inhibition of viral replication. When a virus infects a cell, it replicates its genetic material and packages it into new virus particles. Preventing the packaging of hA3G may contribute to the persistence, dissemination, and the potentially lethal nature of the virus.
The researchers, led by David Derse, Ph.D., in the HIV Drug Resistance Program at NCI's Center for Cancer Research in Frederick, Md., found that by mutating certain amino acids in the virus capsid, or core protein, increased levels of hA3G were incorporated into virus particles. This, in turn, strengthened the ability of hA3G to inactivate the virus. Non-mutated virus particles maintained their resistance to hA3G.
"This finding should aid researchers in their basic understanding of the mechanisms of circumventing viral longevity, and possibly assist in preventing some types of cancer," said NCI Director John E. Niederhuber, M.D.